An experimental treatment model using allogeneic bone marrow transplantation (i.e., adoptive immunotherapy) in combination with chemoradiotherapy for the treatment of a spontaneous leukemia in mice has been developed. The unique feature of the treatment model is the use of intestinal decontamination and isolation in a protective environment to prevent secondary disease. The experimental treatment model uses AKR mice diagnosed as having spontaneous acute T cell lymphoblastic leukemia in an advanced stage. Allogeneic bone marrow transplantation resulted in a significant prolongation of survival time of leukemic animals, prevented development of recurrent leukemia and achieved a significant proportion of "cures". This successful therapeutic model offers a unique opportunity to examine the mechanism(s) behind curative adoptive immunotherapy. We propose to use our treatment model in order to a) determine the relative importance of chemoradiotherapy in decreasing the tumor burden which adoptive immunotherapy must eliminate, b) ascertain the kinetics and site(s) of leukemia recurrence following chemoradiotherapy without immunotherapy, c) characterize the nature of the effector cells responsible for the adoptive immunotherapeutic reaction, d) follow the evolution of the immune response to leukemic and host antigens using in vivo and in vitro measures of antitumor and antihost reactivity, e) correlate the development and/ or abrogation of antihost and antitumor reactivity with susceptibility of leukemia-cured chimeras to donor and host derived leukemias, f) delineate the relative role of leukemia-associated antigens present on normal host cells in susceptibility to the graft-versus-host reaction, and g) test the immune responses of leukemia-cured chimeras in assays of immunocompetence. The proposed studies should contribute significant information regarding the immunological reaction against cancer and methods for sucessfully applying immunotherapy to advanced disease.